University of South Carolina

Research

Research Interests: Organic chemists use C-C bond forming strategies to elaborate molecules generating a myriad of compounds. Nature uses amides and phosphoamides to organize huge arrays of nanomaterials. We are interested in developing predictable supramolecular chemistry using non-covalent urea-urea interactions to build an array of structures and materials with a diverse array of applications.

The study of enzymes has demonstrated that reactions carried out in confined environments proceed with extraordinary efficiency and selectivity. However, the development of synthetic reaction environments has been very challenging. We have identified bis-urea macrocyclic building blocks that predictably assemble to form porous crystalline materials (Figure 1). It is constructed from molecular units (bis-urea macrocycles) that are readily synthesized from rigid spacers and protected ureas. These macrocycles self-assembly one on top of each other by the urea hydrogen bonding motif and by aryl stacking to give functional materials that depend on the size of the macrocycle. For example, macrocycles that contain no cavity (Figure 1a) assemble to give strong pillars. Macrocycles with sizeable cavities (5-10 Å) assemble to give columns with accessible channels (Figure 1b). These columns subsequently pack together to form porous crystals with aligned one-dimensional channels. The dimensions of the homogeneous channels are controlled by the size of the macrocyclic units, which allows for precise and rational control over cavity dimensions, shape, and functionality. Strong pillars with external functional groups such as basic lone pairs (Figure 1c) afford materials that can expand like clays to accept guests in the flexible binding site in between the pillars. This simple approach is remarkably powerful and can precisely and rationally control the synthesis of functional tubular structures. The goal of our research is to understand and apply this supramolecular assembly strategy to generate homogeneous microporous materials for use as confined environments for a wide range of chemical reactions.

We are investigating the utility of these functional porous materials to absorb, transport and organize guests as well as their ability to facilitate the subsequent photoreactions of these encapsulated molecules. Each hosts is crystallized from a suitable solvent (DMSO, DMF, hot AcOH) and self-assembles into columnar structures. If the host contains a sizeable interior cavity than the interior columns contain the solvent of crystallization (Figure 2a). Heating removes this solvent and the empty hosts can be readily loaded with new guests simply by vapor loading or by soaking directly in the liquid guest or in a solution of the liquid guest (Figure 2b). Hosts 2, 4, and 5 show strong preferences for binding polar guests that are matched to the size and shape of their channels.

Figure 2. Absorption of guests by porous bis-urea hosts. a) Schematic depiction of the desorption of solvent followed by exposure to a new guest to form a second host:guest complex. b) Loading can be accomplished by soaking the empty host crystals in the neat liquid guest or in a solution that contains the guest or by exposing the host crystals to the guest vapor. The table shows examples of hosts:guest complexes formed by host 2, 4, and 5. (from Acc. Chem. Res. 2014.)

Reactions in confined environments. We are investigating the use of these porous hosts as ‘stoichiometric’ containers in the solid-state to facilitate photoreactions and oxidations as well as examining them as catalysts in solution. This two-fold approach has several advantages. Characterization of the solid-state complexes allows us to probe how confinement in the channel influences the mechanism, product distribution, yield and selectivity for a specific reaction. Photoreactions and oxidations provide controlled model systems to test how effectively we can probe the effects of confinement on reactions. Ultimately, a better understanding of a reaction mechanism aids in the optimization of conditions and in the development of catalysts. Currently, we are examining the effects of binding on the outcome of bimolecular reactions ([2+2]-cycloadditions and singlet oxygen ene reactions). For example, phenylether host 4 has a zig-zag shaped channel (Figure 3a and b) that facilitates the [2+2]-cycloaddition of enone guests such as 3-methyl-2-cyclopentenone and 2-cyclohexenone in high yield and with high selectivity for the exo head-to-tail dimer (Figure 3c). We study the scope and application of these hosts as catalysts, and investigate the use of micro/nanocrystalline host suspensions in solutions for mediating oxidations of alkenes by singlet oxygen. Our goal is to expand to base-catalyzed reactions and polymerizations.

Inhibitor Development/Drug Discovery.In collaboration with Maks Chruszcz's group, we are working on several joint projects that aim to develop inhibitors for bacterial proteins originating from Vibrio Vulnificus and Wolbachia species. Antimicrobial resistance is a major concern and mounting public health threat. We are part of a team that is focused on developing antimicrobial compounds to target lysine biosynthesis, one of the pathways that is used by bacteria to covalently link peptidoglycan monomers in the bacterial cell wall. One of the current proteins that our group is focused on is inhibiting DapB, a protein which catalyzes NADH or NADPH dependent reduction of the unsaturated bond in L-2,3-dihydrodipicolinate to generate L-tetrahydrodipicolinate. Our groups are studying the feasibility of developing a robust assay to monitor DabB activity as well as developing new inhibitors. The Chruszcz's group are experts in Structural Biology and Macromolecular Crystallography. Our group contributes expertise in molecular modeling, particularly at evaluating interactions that orient molecules in confined spaces, as well as the design and synthesis of new substrates. Porous Polydiacetylene (PDA) Nanofibers.

Our group has been exploring the assembly of a macrocyclic monomer that contains two diacetylene units. These materials can be crystallized under a number of conditions to form columnar structures. The assembled dihydrate of this material (Figure 4) undergoes a single-crystal-to-single-crystal polymerization to give an unusual polydiacetylene (PDA) that consists of a covalent nanotube that has two parallel and aligned PDA chains that run down opposite sides of the tube. The interior channel is defined by the size of the macrocycle. Each PDA covelent nanotube is connected with four neighboring tubes via hydrogen bonding. Such well-ordered PDA crystals and nanofibers may have be of intrest for forming highly conductive organic materials. PDAs can undergo singlet fission and my be of interest for excitonic photovoltaic devices. We are currently investigating these materials in collaboration with Andrew Greytak's group in Chemistry and with Miao Yu's group in Chemical Engineering.

Figure 4. The assembled dihydrate macrocycle can be polymerized in an SCSC process to give a PDA crystal (190 °C for 3 h). View along a single column. Intrapolymeric hydrogen bonds shown as red dashed lines. (Cryst. Growth Des. 2014).